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Pulmonary drug delivery

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https://www.readbyqxmd.com/read/29148851/airway-geometry-airway-flow-and-particle-measurement-methods-implications-on-pulmonary-drug-delivery
#1
A Kourmatzis, S Cheng, H-K Chan
The effectiveness of drug delivery to the lungs is inextricably linked to the fundamental interactions that occur between particles and flow in the extrathoracic airway. Research in this field requires time resolved in-vivo and in-vitro measurements of three separate, yet intricately linked parameters: i) airway flow, ii) airway geometry, and iii) drug particle characteristics. A number of recent significant developments have been made in the experimental diagnostic tools used to characterise these parameters...
November 17, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29138462/the-antibacterial-and-anti-inflammatory-activity-of-chicken-cathelicidin-2-combined-with-exogenous-surfactant-for-the-treatment-of-cystic-fibrosis-associated-pathogens
#2
Brandon J H Banaschewski, Brandon Baer, Christina Arsenault, Teah Jazey, Edwin J A Veldhuizen, Johan Delport, Tracey Gooyers, James F Lewis, Henk P Haagsman, Ruud A W Veldhuizen, Cory Yamashita
Cystic fibrosis (CF) is characterized by recurrent airway infections with antibiotic-resistant bacteria and chronic inflammation. Chicken cathelicin-2 (CATH-2) has been shown to exhibit antimicrobial activity against antibiotic-resistant bacteria and to reduce inflammation. In addition, exogenous pulmonary surfactant has been suggested to enhance pulmonary drug delivery. It was hypothesized that CATH-2 when combined with an exogenous surfactant delivery vehicle, bovine lipid extract surfactant (BLES), would exhibit antimicrobial activity against CF-derived bacteria and downregulate inflammation...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138045/cyclodextrins-structure-physicochemical-properties-and-pharmaceutical-applications
#3
Phatsawee Jansook, Noriko Ogawa, Thorsteinn Loftsson
Since their discovery over 100 years ago cyclodextrins (CDs) have been the subject of numerous scientific publications. In 2016 alone CDs were the subject of over 2200 research articles published in peer-reviewed journals and mentioned in over 2300 patents and patent applications, many of which were on pharmaceutical applications. Natural CDs and their derivatives are used as enabling pharmaceutical excipients that enhance aqueous solubility of poorly soluble drugs, increase drug permeability through biological membranes and improve drug bioavailability...
November 11, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29130758/proniosomes-derived-niosomes-recent-advancements-in-drug-delivery-and-targeting
#4
Maryam Khatoon, Kifayat Ullah Shah, Fakhar Ud Din, Shefaat Ullah Shah, Asim Ur Rehman, Naz Dilawar, Ahmad Nawaz Khan
Vesicular drug delivery systems have gained wide attention in the field of nanotechnology. Among them proniosomes become the superior over other vesicular carriers. Proniosomes are dry formulations of water soluble nonionic surfactant coated carrier system which immediately forms niosomes upon hydration. They have the capability to overcome the instability problems associated with niosomes and liposomes and have the potential to improve solubility, bioavailability, and absorption of various drugs. Furthermore, they offer versatile drug delivery concept for enormous number of hydrophilic and hydrophobic drugs...
2017: Drug Delivery
https://www.readbyqxmd.com/read/29125064/pulmonary-aerosol-delivery-and-the-importance-of-growth-dynamics
#5
Allen E Haddrell, David Lewis, Tanya Church, Reinhard Vehring, Darragh Murnane, Jonathan P Reid
Aerosols are dynamic systems, responding to variations in the surrounding environmental conditions by changing in size, composition and phase. Although, widely used in inhalation therapies, details of the processes occurring on aerosol generation and during inhalation have received little attention. Instead, research has focused on improvements to the formulation of the drug prior to aerosolization and the resulting clinical efficacy of the treatment. Here, we highlight the processes that occur during aerosol generation and inhalation, affecting aerosol disposition when deposited and, potentially, impacting total and regional doses...
December 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/29111673/nano-into-micro-formulations-of-tobramycin-for-the-treatment-of-pseudomonas-aeruginosa-infections-in-cystic-fibrosis
#6
Barbara Porsio, Maria Grazia Cusimano, Domenico Schillaci, Emanuela Fabiola Craparo, Gaetano Giammona, Gennara Cavallaro
Here, nano into micro formulations (NiMs) of tobramycin for the treatment of Pseudomonas aeruginosa airway infections in cystic fibrosis (CF) are described. NiMs were produced by spray drying a solution containing polymers or sugars and a nanometric Polyanion-Tobramcyin Complex (PTC), able to achieve a prolonged antibiotic release. NiMs properties were compared to TOBI®Podhaler®(Novartis), the only one commercially available dry powder inhalatory formulation based on porous microparticles. Produced NiMs showed adequate characteristics for pulmonary administration, as spherical shape, micrometric size and high cytocompatibility towards human bronchial epithelial cells...
November 7, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29107995/the-intratracheal-administration-of-locked-nucleic-acid-containing-antisense-oligonucleotides-induced-gene-silencing-and-an-immune-stimulatory-effect-in-the-murine-lung
#7
Yasunori Uemura, Kenji Hagiwara, Katsuya Kobayashi
Locked nucleic acid containing antisense oligonucleotides (LNA-ASOs) have the potential to modulate the disease-related gene expression by the RNaseH-dependent degradation of mRNAs. Pulmonary drug delivery has been widely used for the treatment of lung disease. Thus, the inhalation of LNA-ASOs is expected to be an efficient therapy that can be applied to several types of lung disease. Because the lung has a distinct immune system against pathogens, the immune-stimulatory effect of LNA-ASOs should be considered for the development of novel inhaled LNA-ASOs therapies...
2017: PloS One
https://www.readbyqxmd.com/read/29096627/a-28-day-randomized-double-blind-placebo-controlled-parallel-group-study-of-nebulized-revefenacin-in-patients-with-chronic-obstructive-pulmonary-disease
#8
Krishna K Pudi, Chris N Barnes, Edmund J Moran, Brett Haumann, Edward Kerwin
BACKGROUND: Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD). In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days' administration of doses up to 700 μg. In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days...
November 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29093369/-development-of-inhalable-dry-powder-formulations-loaded-with-nanoparticles-maintaining-their-original-physical-properties-and-functions
#9
Tomoyuki Okuda
 Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29068693/in-vivo-pulmonary-delivery-and-magnetic-targeting-of-dry-powder-nano-in-microparticles
#10
Dominique N Price, Loreen R Stromberg, Nitesh K Kunda, Pavan Muttil
This brief communication evaluates the cytotoxicity and targeting capability of a dry powder chemotherapeutic. Nano-in-microparticles (NIMs) are a dry powder drug delivery vehicle containing superparamagnetic iron oxide nanoparticles (SPIONs) and either doxorubicin (w/w solids) or fluorescent nanospheres (w/v during formulation; as a drug surrogate) in a lactose matrix. In vitro cytotoxicity was evaluated in A549 adenocarcinoma cells using MTS and LDH assays to assess viability and toxicity after 48 hours of NIMs exposure...
October 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29063794/critical-physicochemical-and-biological-attributes-of-nanoemulsions-for-pulmonary-delivery-of-rifampicin-by-nebulization-technique-in-tuberculosis-treatment
#11
Kifayatullah Shah, Lai Wah Chan, Tin Wui Wong
The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29058607/aerosol-delivery-during-invasive-mechanical-ventilation-a-systematic-review
#12
Jonathan Dugernier, Stephan Ehrmann, Thierry Sottiaux, Jean Roeseler, Xavier Wittebole, Thierry Dugernier, François Jamar, Pierre-François Laterre, Gregory Reychler
BACKGROUND: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed. METHODS: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias...
October 21, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29047275/excipient-free-pulmonary-delivery-and-macrophage-targeting-of-clofazimine-via-air-jet-micronization
#13
Ashlee D Brunaugh, Syed Umer Jan, Silvia Ferrati, Hugh D C Smyth
Clofazimine (CFZ) is highly active against mycobacterium, including resistant Mycobacterium tuberculosis, but its therapeutic efficacy via the oral route is limited by severe adverse effects, poor aqueous solubility, and slow onset of action. Pulmonary delivery of CFZ is an attractive alternative to target mycobacterium-harboring alveolar macrophages. This study explores the use of air jet milling to develop a respirable, cost-effective CFZ formulation. Jet milled CFZ was readily dispersed from an off-the-shelf dry powder inhaler without the need for additional excipients or carrier particles...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29046368/enhancement-of-lung-gene-delivery-after-aerosol-a-new-strategy-using-non-viral-complexes-with-antibacterial-properties
#14
Angelique Mottais, Tony Le Gall, Yann Sibiril, Julian Ravel, Véronique Laurent, Frédérique d'Arbonneau, Tristan Montier
The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis, leads to the development of chronic infections in the respiratory tract. Thus, the symptomatic management of the disease requires, in particular, repetitive antibiotherapy. Besides these antibacterial treatments, certain pathologies, such as cystic fibrosis or chronic obstructive pulmonary disease, require the intake of many drugs. This simultaneous absorption may lead to undesired drug interactions. For example, Orkambi® (lumacaftor/Ivacaftor, Vertex), a pharmacological drug employed to treat F508del patients, cannot be used with antibiotics such as rifampicin or rifabutin (rifamycin family) which are necessary to treat Mycobacteriaceae...
October 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29035148/treatment-of-pulmonary-fibrosis-with-sirna-against-a-collagen-specific-chaperone-hsp47-in-vitamin-a-coupled-liposomes
#15
Mitsuo Otsuka, Masanori Shiratori, Hirofumi Chiba, Koji Kuronuma, Yasushi Sato, Yoshiro Niitsu, Hiroki Takahashi
BACKGROUND: Pulmonary fibrosis is a life-threatening pathological state of progressive interstitial lung diseases, such as idiopathic pulmonary fibrosis. Myofibroblasts are known to play a critical role in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the inhibitory effect of a small interfering RNA (siRNA) on a collagen-specific chaperone heat shock protein 47 (HSP47). The siRNA was preferentially delivered to myofibroblasts in a bleomycin (BLM)-induced pulmonary fibrosis rat model using siRNA against HSP47, encapsulated in a vitamin A-coupled liposome (VA-lip-siRNA HSP47)...
October 16, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/29031573/aerosol-furosemide-for-dyspnea-controlled-delivery-does-not-improve-effectiveness
#16
Capucine Morélot-Panzini, Carl R O'Donnell, Robert W Lansing, Richard M Schwartzstein, Robert B Banzett
Aerosolized furosemide has been shown to relieve dyspnea; nevertheless, all published studies have shown great variability in response. This dyspnea relief is thought to result from the stimulation of slowly adapting pulmonary stretch receptors simulating larger tidal volume. We hypothesized that better control over aerosol administration would produce more consistent dyspnea relief; we used a clinical ventilator to control inspiratory flow and tidal volume. Twelve healthy volunteers inhaled furosemide (40mg) or placebo in a double blind, randomized, crossover study...
October 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29022837/critical-parameters-for-particle-based-pulmonary-delivery-of-chemotherapeutics
#17
Ali Dabbagh, Noor Hayaty Abu Kasim, Chai Hong Yeong, Tin Wui Wong, Noorsaadah Abdul Rahman
Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery...
October 12, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29022772/formulation-and-delivery-strategies-of-ibuprofen-challenges-and-opportunities
#18
Jake Irvine, Afrina Afrose, Nazrul Islam
Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects...
October 12, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29016769/safety-and-efficiency-of-porous-tip-contact-force-catheter-for-drug-refractory-symptomatic-paroxysmal-atrial-fibrillation-ablation-results-from-the-smart-sf-trial
#19
Larry A Chinitz, Daniel P Melby, Francis E Marchlinski, Craig Delaughter, Robert S Fishel, George Monir, Anshul M Patel, Douglas N Gibson, Charles A Athill, Lee Ming Boo, Robert Stagg, Andrea Natale
Aims: THERMOCOOL SMARTTOUCH® SF Catheter is a new contact-force (CF)-sensing catheter with 56-hole porous tip designed for improved cooling and reduced fluid delivery compared with a standard 6-hole open-irrigated catheter. The SMART SF study examined the periprocedural safety, acute effectiveness, and procedural efficiency of the catheter for drug-refractory symptomatic paroxysmal atrial fibrillation (PAF) ablation. Methods and results: The prospective, open-label, non-randomized SMART-SF was conducted at 17 US sites...
August 9, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28992055/amphotericin-b-concentrations-in-healthy-mallard-ducks-anas-platyrhynchos-following-a-single-intratracheal-dose-of-liposomal-amphotericin-b-using-an-atomizer
#20
Ashley Phillips, Christine V Fiorello, Rachel M Baden, Jack H Liu, Nathaniel C Burmas, Carlos A Ruvalcaba, Roger Monroy, F Charles Mohr, Ronette Gehring, Jean-Pierre Delplanque, Karl V Clemons, David A Stevens, Lisa A Tell
Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3 mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos)...
August 3, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
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